Chemical nose could provide more accurate indication of cancer than
biomarkers

8 July 2009

Your browser does not support inline frames or is currently configured not to display inline frames.
Using a 'chemical nose' array of nanoparticles and polymers,
researchers at the University of Massachusetts Amherst have developed a
fundamentally new, more effective way to differentiate not only between
healthy and cancerous cells but also between metastatic and
non-metastatic cancer cells.

It’s a tool that could revolutionize cancer detection and treatment,
according to chemist Vincent Rotello and cancer specialist Joseph Jerry
in an article in the June 23 issue of the journal Proceedings of the
National Academy of Sciences online.

Currently, detecting cancer via cell surface biomarkers has taken
what’s known as the “lock and key” approach. Drawbacks of this method
include that foreknowledge of the biomarker is required. Also, as
Rotello explains, a cancer cell has the same biomarkers on its surface
as a healthy cell, but in different concentrations, a maddeningly small
difference that can be very difficult to detect. “You often don’t get a
big signal for the presence of cancer,” he notes. “It’s a subtle thing.”

He adds, “Our new method uses an array of sensors to recognize not
only known cancer types, but it signals that abnormal cells are present.
That is, the chemical nose can simply tell us something isn’t right,
like a ‘check engine light,’ though it may never have encountered that
type before.” Further, the chemical nose can be designed to alert
doctors of the most invasive cancer types, those for which early
treatment is crucial.

Nanoparticles and polymers were used
to create a sensor that can distinguish between
healthy, cancerous and metastatic cells

In blinded experiments in four human cancer cell lines (cervical,
liver, testis and breast), as well as in three metastatic breast cell
lines, and in normal cells, the new detection technique correctly
indicated not only the presence of cancer cells in a sample but also
identified primary cancer vs. metastatic disease.

In further experiments to rule out the possibility that the chemical
nose had simply detected individual differences in cells from different
donors, the researchers repeated the experiments in skin cells from
three groups of cloned BALB /c mice: healthy animals, those with primary
cancer and those with metastatic disease. Once again, it worked. “This
result is key,” says Rotello. “It shows that we can differentiate
between the the three cell types in a single individual using the
chemical nose approach.”

Rotello’s research team, with colleagues at the Georgia Institute of
Technology, designed the new detection system by combining three gold
nanoparticles that have special affinity for the surface of chemically
abnormal cells, plus a polymer known as PPE, or para-phenyleneethynylene.
As the ‘check engine light,’ PPE fluoresces or glows when displaced from
the nanoparticle surface.

By adding PPE bound with gold nanoparticles to human cells incubating
in wells on a culture plate, the researchers induce a response called
“competitive binding”. Cell surfaces bind the nanoparticles, displacing
the PPE from the surface. This turns on PPE’s fluorescent switch. Cells
are then identified from the patterns generated by different
particle-PPE systems.

Rotello says the chemical nose approach is so named because it works
like a human nose, which is arrayed with hundreds of very selective
chemical receptors. These bind with thousands of different chemicals in
the air, some more strongly than others, in the endless combination we
encounter. The receptors report instantly to the brain, which recognizes
patterns such as, for example, “French fries,” or it creates a new smell
pattern.

Chemical receptors in the nose plus the brain’s pattern recognition
skills together are incredibly sensitive at detecting subtly different
combinations, Rotello notes. We routinely detect the presence of tiny
numbers of bacteria in meat that’s going bad, for instance. Like a human
nose, the chemical version being developed for use in cancer also
remembers patterns experienced, even if only once, and creates a new one
when needed.

For the future, Rotello says further studies will be undertaken in an
animal model to see if the chemical nose approach can identify cell
status in real tissue. Also, more work is required to learn how to train
the chemical nose’s sensors to give more precise information to
physicians who will be making judgment calls about patients’ cancer
treatment. But the future is promising, he adds. “We’re getting complete
identification now, and this can be improved by adding more and
different nanoparticles. So far we’ve experimented with only three, and
there are hundreds more we can make.”